Synthesis, characterization, and anti-inflammatory activity of tetrahydropiperine, piperic acid, and tetrahydropiperic acid via down regulation of NF-κB pathway.

[Display omitted] • Tetrahydropiperic acid (THPA) can effectively attenuate the inflammatory response, both in-vitro and in-vivo suggesting, THPA as a potential novel anti-inflammatory drug candidate in the treatment of inflammatory disorders. • THPA significantly decreased the production of NO and pro-inflammatory cytokines (IL-6, IL-1β & TNF-α) in LPS stimulated RAW 264.7 macrophages and in-vivo experimental model. • THPA effectively decreased carrageenan-induced paw edema and showed protective effect in LPS challenged mice. • The anti-inflammatory potential of THPA is attributed to downregulation of NF-κB signaling pathway. The present study describes the synthesis, characterization, and evaluation of tetrahydropiperine (THP), piperic acid (PA), and tetrahydropiperic acid (THPA) as anti-inflammatory agents. THPA demonstrated potent anti-inflammatory activity among all the compounds. The anti-inflammatory potential was investigated in both in-vitro and in-vivo experimental models. Our findings demonstrated that THPA effectively suppressed the production of pro-inflammatory mediators, including nitric oxide and pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in both in vitro and in vivo. Additionally, THPA attenuated the expression of i-NOS and COX-2 in RAW 264.7 macrophages. The oral administration of THPA significantly reduced carrageenan induced paw edema thickness and alleviated liver, lung, and kidney injury induced by LPS. THPA also reduced the infiltration of inflammatory cells, prevented the occurrence of significant lesions, and mitigated tissue damage. Moreover, THPA significantly improved the survival rate of mice challenged with LPS. Our western blot studies also found that LPS induced NF-κB activation was downregulated by treatment with THPA in an in vivo system. These results collectively illustrated the potential of THPA as a therapeutic agent for treating inflammatory diseases. [ABSTRACT FROM AUTHOR]